The Ohio State University
Medical Center
Clinical Practice Guidelines
Transfusions in Adults
Definitions of Recommendation Levels
(The quality of evidence determines the strength of the guideline.)
Quality of Evidence
Level of Evidence
I
Good
II
Fair
III
Poor
Definition
Evidence obtained from at least one properly randomized controlled trial or from welldesigned cohort or case-control analytic studies, preferably from more than one center or
research group, or national consensus panel recommendations based on controlled,
randomized studies.
Evidence obtained from multiple time series with or without intervention, or national
consensus panel recommendations based on uncontrolled studies with positive outcomes or
based on studies showing dramatic effects of an intervention.
Opinions of respected authorities, based on clinical experience, descriptive studies, or reports
of expert committees.
Strength of Recommendation
A
Strength
It is advised that this be done.
..
B
This may be done . . .
B1
It should be done in most
cases.
It should NOT be done in
most cases.
It is advised that this NOT be
done . . .
Definition
in a periodic health examination, or a diagnostic maneuver should be
done, or treatment of a medical problem should be given. There is
good evidence (level I) to support the recommendation.
in a periodic health examination, or a diagnostic maneuver may be
done, or treatment of a medical problem may be given.
There is fair evidence (level II) to support the recommendation.
There is poor evidence (level III) regarding the recommendation, which
may be made on other grounds.
in a periodic health examination, or a diagnostic maneuver should not
C
be done, or treatment of a medical problem should not be given. There
is good evidence (level I) to support the recommendation that this not
be done.
Note: Practice guidelines are not standards that are meant to be applied rigidly and followed in virtually all cases.
Patient choice and physician judgment must remain central to the selection of diagnostic tests and therapy. Practice
guidelines should be helpful to physicians and patients alike in making their decisions. At the Ohio State University
Medical Center, clinical practice guidelines are reviewed annually to incorporate new evidence.
B2
Guideline Statement
("B1" Recommendation: This should be done in most cases.
There is fair evidence [Level II] to support the recommendation.)
Patients should be evaluated for blood component therapy by clinical and laboratory assessment. The appropriate
blood component is selected and given in the appropriate dose.
Objective
To define the appropriate use of blood components for transfusion therapy.
Key Words
blood, blood products, transfusion
Background Information
RED BLOOD CELLS
The main purpose of red blood cell transfusion is to increase oxygen-carrying capacity. However, the critical
hemoglobin level requiring transfusion is unclear. Animal data indicate that hemoglobin levels of 3-5 g/dl are
critical; below those levels, decompensation for the anemia occurs. For healthy humans, the hemoglobin level for
decompensation is similar at something less than 5 g/dl. One study deliberately bled patients and volunteers to
hemoglobin levels < 5.0 g/dl without clinical sequelae.1 Several randomized clinical trials have shown no
differences in outcome whether the transfusion triggers were high or low. One recent large random controlled trial
(RCT) showed that mortality was less for those critically ill patients who received red blood cells for hemoglobin
levels < 7.0 g/dl than for those transfused to maintain the hemoglobin > 10 g/dl. 2 Patients with cardiac disease
showed no differences in outcomes in this study.
Another study of elderly patients > 60 years of age showed that transfusion had no effect on mortality as long as the
hemoglobin level was > 8 g/dl.3 Two studies of Jehovah’s Witnesses showed that mortality did not increase for
hemoglobin < 5 g/dl, even for cardiovascular patients.4, 5 One patient with postoperative hemoglobin of 2.7 g./dl
survived.
Recent published guidelines have cautioned against a uniform hemoglobin level as an indication for red blood cell
transfusion. The American Society of Anesthesiologists Task Force on Blood Component Therapy6 as well as the
Red Blood Cell Administration Practice Guideline Development Task Force of the College of American
Pathologists7 recommend that transfusion is rarely indicated when the hemoglobin level is > 10 g/dl, and almost
always indicated when the hemoglobin level is < 6 g/dl. If the hemoglobin level is between 6 and 10 g/dl,
transfusions should be "based on the patient’s risk for complication of inadequate oxygenation." 6, 7 In acute
hemorrhage, the hemoglobin level may not reflect the severity of hemorrhage nor the true amount of blood loss.
Other considerations to limit or avoid transfusions include careful surgical hemostasis, limiting blood loss for
laboratory assays, use of specific pharmacological agents in chronic anemia (e.g., vitamins, erythropoietin), reducing
risk of hemorrhage caused by many types of drugs (e.g., aspirin, warfarin, heparin), and correcting any existing
coagulopathy.
PLATELETS
The purpose of platelet transfusion is to treat clinically significant thrombocytopenia and treat hemorrhage caused
by thrombocytopenia or platelet functional disorders. In the absence of clinically significant hemorrhage, the
customary platelet count triggering platelet transfusion has been 20,000/μl. However, several authors have evidence
for a lower transfusion trigger, such as 5,000/μl or 10,000/μl in stable patients. 8,9,10,11 Patients with concomitant
conditions, such as sepsis, antibiotic therapy, and other abnormalities of hemostasis, may require higher transfusion
triggers. For hemorrhage or invasive procedures, the recommended level is 50,000/μl. 12,13
Two platelet preparations are available: platelet concentrates prepared from whole blood, and platelets collected by
apheresis. For most blood suppliers, 4-6 units (bags) of platelet concentrates are equal to one plateletpheresis.
Platelet donors may be selected for their CMV status, HLA type, or platelet crossmatch compatibility, as well as
ABO and Rh types.
Patients who have poor posttransfusion platelet recovery and survival present challenges for platelet therapy. 14,15
Sepsis, hypersplenism, fever, DIC, amphotericin, hemorrhage, ABO mismatch, and alloimmunization affect platelet
recovery and survival. The cause of poor platelet recovery and survival in most patients is nonimmune. A trial of
ABO matched and fresh (less than 3 days old) platelet products for transfusion can be worthwhile. For
alloimmunized patients, antibodies may be HLA and/or platelet specific. HLA matching requires HLA typing for the
patient and donor, and collection, processing, and delivery of the plateletpheresis product. On the other hand,
platelet crossmatching can be performed on platelet products in inventory. Because of this, platelet crossmatched
products are more readily available.
FRESH FROZEN PLASMA
Fresh frozen plasma (FFP) is transfused to correct hemostatic abnormalities. Generally, hemostasis is adequate when
coagulation factors are at least 20-30% of normal and fibrinogen is greater than 75 mg/dl. Bleeding is generally
associated with PT and/or PTT values greater than 1.5 to 1.8 times normal during surgery or massive transfusion. 16,17
However, abnormal PT and PTT values up to 2.0 times normal are poor predictors of bleeding associated with minor
invasive procedures such as paracentesis, thoracentesis, percutaneous liver biopsy, and central venous
catheterizations.18,19,20
In addition, expert opinion does not support the use of FFP to reverse warfarin effect associated with bleeding or
before invasive procedures if the INR is < 1.8.21,22 For surgery, expert opinion supports holding one or more doses of
warfarin or administering low-dose vitamin K (2-4 mg orally) and using postoperative prophylaxis with low
molecular weight heparin and warfarin. 23Generally, massive transfusion is not accompanied by excessive bleeding
until more than one blood volume is replaced. Correcting thrombocytopenia has been shown to be of greater
importance in excessive microvascular bleeding than correcting PT and PTT prolongation.23
For patients receiving heparin, protamine sulfate, rather than FFP, should be used to correct prolonged PTT.
CRYOPRECIPITATE-POOR PLASMA
Cryoprecipitate-poor plasma (also called cryo-poor plasma) is the supernatant remaining after separation of
cryoprecipitate. The high-molecular-weight von Willebrand factor is removed in this process. As high-molecularweight von Willebrand factor is present in hemolytic uremic syndrome and thrombotic thrombocytopenia purpura,
cryo-poor plasma and solvent detergent (SD)-treated plasma (see below) are preferred for therapy of these
diseases.25 Cryoprecipitate-poor plasma may be used as a direct infusion in patients with TTP/HUS or as the
replacement fluid during therapeutic plasma exchange (plasmapheresis.)
SOLVENT-DETERGENT (SD)-TREATED PLASMA
Solvent-detergent-treated plasma is prepared from large pools of fresh frozen plasma, cleared of the solvent and
detergent, filtered, and transferred in 200 ml aliquots to bags, which are again frozen. The solvent-detergent
treatment is effective against lipid enveloped viruses such as HIV and hepatitis B and C in the donor plasma.
Disadvantages are the smaller volume compared to FFP (200 ml vs. 250-300 ml), possible decreased hemostatic
effectiveness, and the higher cost per bag.
CRYOPRECIPITATE
Cryoprecipitate is rich in factor VIII, fibrinogen, von Willebrand factor, and factor XIII. However, factor
concentrates, treated to be virally safe, are available for treatment of factor VIII deficiency and von Willebrand
disease. Factor XIII is a rare deficiency. Therefore, cryoprecipitate is used to treat hypofibrinogenemia and as a
source for fibrin glue. There is little scientific evidence about the effectiveness of cryoprecipitate in the treatment of
hypofibrinogenemia; however, expert opinion agrees that cryoprecipitate is likely to be effective when used to
correct fibrinogen levels < 80 mg/dl.6
SPECIAL PRODUCTS
Leukocyte-Reduced Red Blood Cells and Platelets
Leukocyte-reduced blood is used to prevent febrile non-hemolytic transfusion reactions in patients with repeated or
severe febrile reactions. Several studies have shown that leukocyte reduction with fourth-generation filters (those in
use currently) are effective in reducing transmission of cytomegalovirus (CMV) by transfusion in premature
neonates and patients with bone marrow or solid organ transplants. 26,27,28 Leukocyte depletion of platelet
transfusions has been shown to reduce the incidence of human leukocyte antigen (HLA) alloimmunization in
patients who are anticipated to receiver repeated platelet transfusions. Similarly, leukocyte depletion of red blood
cells may reduce HLA alloimmunization in patients waiting for organ transplantation.
Many studies have examined the effect of transfusion on cancer recurrence, metastasis, and mortality. A pooled
analysis of 20 studies showed that if an adverse effect exists, it has to be small. 29 Posttransfusion infections have
been studied, with rates of infection about 20-30% with allogeneic transfusion versus about 0-10% with autologous
transfusion.30 A large prospective trial did not show a reduction in length of stay for cardiac surgery patients
receiving leukocyte-reduced blood. Another concern has been new variant Creutzfeldt-Jacob disease (nvCJD).
Prions have been found in human lymphocytes, granulocytes, platelets, and plasma. However, no evidence has been
found that CJD has been transmitted by blood transfusion.
Cytomegalovirus (CMV) Seronegative Red Blood Cells and Platelets
Donor CMV status is important for premature infants, seronegative recipients of solid organ and autologous bone
marrow transplants, and all allogeneic bone marrow transplant recipients. CMV disease in these patients can be
severe and life threatening.
Only about 40% of the donor population in this area is CMV seronegative. Therefore, CMV seronegative RBC and
platelets are in short supply. Leukocyte-reduced blood products are equally effective as seronegative blood products
in preventing CMV transmission.
Gamma Irradiation
Transfusions-associated graft-versus-host disease (TA-GVHD) is caused by donor lymphocytes proliferating in the
recipient. The risk of the disease is increased for patients who are immunosuppressed (bone marrow transplant,
Hodgkin’s disease) and those with immature immune systems (low birth weight neonates). However TA-GVHD has
also been reported in immunocompetent patients, especially those receiving fresh blood or blood from blood
relatives. TA-GVHD can be prevented by gamma irradiation of cellular blood products.
ADVERSE REACTIONS
The most common adverse transfusion reactions are febrile reactions, urticarial reactions, and volume overload.
Febrile reactions can be treated and prevented by antipyretics such as acetaminophen; urticarial reactions respond to
diphenhydramine. Rarer are the hemolytic reactions. The most common symptom of hemolytic transfusion reaction
is fever; therefore, fever in a patient receiving RBC transfusion should be investigated to rule out a hemolytic
reaction.
Another rare, but serious, reaction is transfusion-related acute lung injury (TRALI), caused by aggregation of
leukocytes in the pulmonary vasculature. Treatment is respiratory support. Most cases resolve in a few days.
Many diseases can be transmitted by blood; however, transmission is generally rare. The estimated risk of
transmission of HIV is < 1:600,000.
Recommendations
Hemoglobin
> 10 g/dL
6.0-10.0 g/dL
< 6.0 g/dL
Acute blood loss > 20% B.V.
Red Blood Cell Transfusion
Recommendation
RBC transfusion rarely needed
RBC needed only for symptomatic patients
RBC transfusion generally needed
Fluid resuscitation; RBC transfusion
Platelets
Acute Hemorrhage or Invasive Procedure
Platelet count < 50,000/ul
Platelet dysfunction unresponsive to other modalities (e.g., DDAVP, dialysis)
Prophylaxis
Stable patient
Platelet count < 10,000/μl
High-risk patient
Platelet count < 20,000/μl
Decreasing platelet count
Platelet count < 20,000/μl in next 24 hours
Rec
B1
B1
B1
B1
Rec.
B1
B1
B1
B1
B1
Fresh Frozen Plasma (FFP)
Active Bleeding or Invasive Procedure
INR > 1.8 (PT > 18 sec.)
APTT > 60 sec. (Use protamine sulfate to correct PTT prolongation due to heparin)
Coagulation factor assay < 25%
Urgent reversal of warfarin (INR > 1.8) (hold dose or low-dose vitamin K preferred)
Multiple coagulation factor deficiency (severe liver disease, DIC, vitamin K depletion)
Other
Plasma exchange for TTP/HUS (second line)
Cryoprecipitate-Poor Plasma
Plasma exchange for TTP/HUS
Rec.
B1
B1
B1
B1
B1
B1
Rec
.
B1
Fibrinogen
< 50 mg/dL
< 100 mg/dL
Cryoprecipitate
Condition
Stable patient
Acute hemorrhage or invasive procedure
von Willebrand’s disease (second line)
Fibrin surgical adhesive
Rec.
B1
B1
B1
B1
Recommendations (Continued)
Leukocyte-Reduced Red Blood Cells and Platelets
Leukocyte-reduced blood transfusion is recommended:
 Patients with severe or repeated febrile non-hemolytic transfusion reactions.
 Patients for whom CMV seronegative red blood cells and platelets are indicated.
 Patients who are anticipated to receive repeated platelet transfusions (to reduce HLA
alloimmunization).
Cytomegalovirus (CMV) Seronegative Red Blood Cells and Platelets
CMV seronegative red blood cells and platelets are recommended for:
 Premature infants, seronegative recipients of solid organ and autologous bone marrow
transplants, and all allogeneic bone marrow transplant recipients
Rec.
B1
B1
B1
B1
Gamma Irradiation
Rec
Gamma irradiation of cellular blood products is recommended for prevention of transfusion-associated graft versus host
disease in:
B1
 Patients who are immunosuppressed (bone marrow transplant, Hodgkin’s disease)
B1
 Patients with immature immune systems (low birth weight neonates)
 Some immunocompetent patients, especially those receiving fresh blood or blood from blood
B1
relatives
Adverse Reactions




Febrile reactions to transfusion
 can be treated and prevented by antipyretics such as acetaminophen
Urticarial reactions
 can be treated with diphenhydramine
Fever in a patient receiving RBC transfusion
 should be investigated to rule out hemolytic reaction
Transfusion-related acute lung injury (TRALI)
 treated with respiratory support